Substituted Pyrrolidinamides III

Description

The invention relates to compounds according to the general formula (I), (I) that act as glucocorticoid receptor modulators and can be used in the treatment and / or prophylaxis of disorders that are at least partially mediated by the glucocorticoid receptor. 1. A compound according to the general formula (I), (I) where R1 represents phenyl; -C1-6-phenyl alkylene; 5- or 6-membered heteroaryl; -C1-6-alkylene (5- or 6-membered heteroaryl) or -C1-10-alkylene; R1? represents H; -C1-10-alkylene; O -CYCLOALKYLOC3-10-; R2 REPRESENTS -C(=O)-ALKYLOC1-10-; -C(=O)-CYCLOALKYLOC3-10-; -C(=O)-ALKYLENEC1-6-CYCLOALKYLOC3-10-; -C(=O)-(3-7 MEMBER HETEROCYCLOYL); -C(=O)-ALKYLENEC1-6-(3-7 MEMBER HETEROCYCLOYL); -C(=O)-PHENYL; -C(=O)-ALKYLENEC1-6-PHENYL; -C(=O)-(5- OR 6 MEMBER HETEROARYL); -C(=O)-ALKYLENEC1-6-(5- OR 6 MEMBER HETEROARYL); -S(=O)1-2-ALKYLOC1-10-; -S(=O)1-2-CYCLOALKYLOC3-10-; -S(=O)1-2-ALKYLENOC1-6-CYCLOALKYLOC3-10-;-S(=O)1-2-(3-7 MEMBERRED HETEROCYCLOYL); -S(=O)1-2-C1-6-ALKYLENE(3-7 MEMBERRED HETEROCYCLOYL); -S(=O)1-2-PHENYL; -S(=O)1-2-C1-6-ALKYLENE(PHENYL); -S(=O)1-2-(5- OR 6 MEMBERRED HETEROARYL); OR -S(=O)1-2-C1-6-ALKYLENE(5- OR 6 MEMBERRED HETEROARYL); R3 AND R3? INDEPENDENTLY OF EACH OTHER REPRESENT H; F; CL; -C1-10-ALKYL; -C3-6-CYCLOALKYL; -CH2-C3-6-CYCLOALKYL; 3- TO 7-MEMBERED HETEROCYCLOYL; -CH2-(3- TO 7-MEMBERED HETEROCYCLOYL); -CH2-PHENYL; OR -CH2-(5- OR 6-MEMBERED HETEROARYL); OR R3 AND R3? TOGETHER WITH THE CARBON ATOM TO WHICH THEY ARE ATTACHED FORM A C3-10-CYCLOYL; OR 3- TO 7-MEMBERED HETEROCYCLOYL; R4 REPRESENTS - PHENYL; -C1-6-PHENYL; 5- OR 6-MEMBERED HETEROARYL; OR -C1-6-PHENYL (5- OR 6-MEMBERED HETEROARYL); A, X, YYZ INDEPENDENTLY OF EACH OTHER REPRESENT NOT CH; WHERE AT LEAST ONE OF R1, R3 AND R3 IS NOT H;WHERE C1-10 ALKYL, AND C1-6 ALKYLENE IN EACH CASE INDEPENDENTLY OF EACH OTHER IS LINEAR OR BRANCHED, SATURATED OR UNSATURATED; WHERE C1-10 ALKYL, C1-6 ALKYLENE, C3-10 CYCLOALKYL AND 3- TO 7-MEMBERED HETEROCYCLOALKYL IN EACH CASE INDEPENDENTLY OF EACH OTHER ARE UNSUBSTITUTED OR MONO- OR POLYSUBSTITUTED WITH ONE OR MORE SUBSTITUENTS SELECTED FROM -F; -CL; -BR; -I; -CN; C1-6 ALKYL; -CF3; -CF2H; -CFH2; -CF2CL; -CFCL2; -C(=O)-C1-6 ALKYL; -C(=O)-OH; -C(=O)-OALKYLOC1-6-; -C(=O)-NH2; -C(=O)-NH(ALKYLOC1-6-); -C(=O)-N(ALKYLOC1-6-)2; -OH; =O; -OCF3; -OCF2H; -OCFH2; -OCF2CL; -OCFCL2; -O-ALKYLOC1-6-; -OC(=O)-ALKYLOC1-6-; -OC(=O)-O-ALKYLOC1-6-; -O-(CO)-NH(ALKYLOC1-6-); -OC(=O)-N(ALKYLOC1-6-)2; -OS(=O)2-NH2; -OS(=O)2-NH(ALKYLOC1-6-); -OS(=O)2-N(ALKYLOC1-6-)2; -NH2; -NH(ALKYLOC1-6-); -N(ALKYLOC1-6-)2; -NH-C(=O)-ALKYLOC1-6-; -NH-C(=O)-O-ALKYLOC1-6-; -NH-C(=O)-NH2; -NH-C(=O)-NH(ALKYLOC1-6-); -NH-C(=O)-N(ALKYLOC1-6-)2; -N(ALKYLOC1-6-)-C(=O)-ALKYLOC1-6-;-N(ALKYLOC1-6-)-C(=O)-O-ALKYLOC1-6-; -N(ALKYLOC1-6-)-C(=O)-NH2; -N(ALKYLOC1-6-)-C(=O)-NH(ALKYLOC1-6-); -N(ALKYLOC1-6-)-C(=O)-N(ALKYLOC1-6-)2; -NH-S(=O)2OH; NH-S(=O)2-ALKYLOC1-6-; -NH-S(=O)2-O-ALKYLOC1-6-; -NH-S(=O)2-NH2; -NH-S(=O)2-NH(ALKYLOC1-6-); -NH-S(=O)2N(ALKYLOC1-6-)2; -N(ALKYLOC1-6-)-S(=O)2-OH; -N(ALKYLOC1-6-)-S(=O)2-ALKYLOC1-6-; -N(ALKYLOC1-6-)-S(=O)2-O-ALKYLOC1-6-; -N(ALKYLOC1-6-)-S(=O)2-NH2; -N(ALKYLOC1-6-)-S(=O)2-NH(ALKYLOC1-6-); -N(ALKYLOC1-6-)-S(=O)2-N(ALKYLOC1-6-)2; -SCF3; -SCF2H; -SCFH2; -S-ALKYLOC1-6-; -S(=O)-ALKYLOC1-6-; -S(=O)2-ALKYLOC1-6-; -S(=O)2-OH; -S(=O)2-O-ALKYLOC1-6-; -S(=O)2-NH2; -S(=O)2-NH(C1-6-ALKYLO); -S(=O)2-N(C1-6-ALKYLO)2; C3-6-CYCLOALKYLO; 3- TO 6-MEMBERED HETEROCYCLOYL; PHENYL; 5- OR 6-MEMBERED HETEROCYCLOYL; -O-C3-6-CYCLOALKYLO; -O-(3- TO 6-MEMBERED HETEROCYCLOYL); -O-PHENYL; -O-(5- OR 6-MEMBERED HETEROCYCLOYL); -C(=O)-C3-6-CYCLOALKYLO; -C(=O)-(3- TO 6-MEMBERED HETEROCYCLOYL); -C(=O)-PHENYL;-C(=O)-(5- OR 6-MEMBERED HETEROARYL); -S(=O)2-(C3-6-CYCLOALKYLO); -S(=O)2-(3- TO 6-MEMBERED HETEROCYCLOAKYL); -S(=O)2-PHENYL OR -S(=O)2-(5- OR 6-MEMBERED HETEROARYL); WHEREIN PHENYL AND 5- OR 6-MEMBERED HETEROARYL IN EACH CASE INDEPENDENTLY OF EACH OTHER ARE UNSUBSTITUTED OR MONO- OR POLY-SUBSTITUTED WITH ONE OR MORE SUBSTITUENTS SELECTED FROM -F; -CL; -BR; -I; -CN; C1-6-ALKYL; -CF3; -CF2H; -CFH2; -CF2CL; -CFCL2; ALKYLENE-C1-4-CF3; ALKYLENE-C1-4-CF2H; ALKYLENE-C1-4-CFH2; -C(=O)-ALKYLOC1-6-; -C(=O)-OH; -C(=O)-OALKYLOC1-6-; -C(=O)-NH(OH); -C(=O)-NH2; -C(=O)-NH(ALKYLOC1-6-); -C(=O)-N(ALKYLOC1-6-)2; -OH; -OCF3; -OCF2H; -OCFH2; -OCF2CL; -OCFCL2; -O-ALKYLOC1-6-; -O-CYCLOALKYLOC3-6-; -O-(3-6 MEMBED HETEROCYCLOALKYL); -NH2; -NH(ALKYLOC1-6-); -N(ALKYLOC1-6-)2; -NH-C(=O)-ALKYLOC1-6-; -N(ALKYLOC1-6-)-C(=O)-ALKYLOC1-6-; -NH-C(=O)-NH2; -NH-C(=O)-NH(ALKYLOC1-6-); -NH-C(=O)-N(ALKYLOC1-6-)2; -N(ALKYLOC1-6-)-C(=O)-NH(ALKYLOC1-6-);-N(C1-6-ALKYLO)-C(=O)-N(C1-6-ALKYLO)2; -NH-S(=O)2-C1-6-ALKYLO; -SCF3; -S-C1-6-ALKYLO; -S(=O)-C1-6-ALKYLO; -S(=O)2-C1-6-ALKYLO; -S(=O)2-NH2; -S(=O)2-NH(C1-6-ALKYLO); -S(=O)2-N(C1-6-ALKYLO)2; C3-6-CYCLOALKYLO; C1-4-ALKYLENE-C3-6-CYCLOALKYLO; 3-6 MEMBER HETEROCYCLOYL; C1-4-ALKYLENE (3-6 MEMBER HETEROCYCLOYL); 5- OR 6-MEMBERED PHENYL OR HETEROARYL; IN THE FORM OF THE FREE COMPOUND OR A PHYSIOLOGICALLY ACCEPTABLE SALT THEREOF. PROVIDED THAT THE FOLLOWING COMPOUNDS ARE EXCLUDED: AMIDE OF N-[(2R,3S)-4,4-DIMETHYL-1-[1-(1-METHYL-6-OXO-1H-PYRIDIN-3-YL)-1H-INDAZOL-5-YL]-5-OXO-2-PHENYL-PYROLIDIN-3-YL]-CYCLOPROPANECARBOXYLIC ACID; N-[(2S,3R)-4,4-DIMETHYL-1-[1-(1-METHYL-6-OXO-1H-PYRIDIN-3-IL)-1H-INDAZOLE-5-IL]-5-OXO-2-PHENYL-PIR ROLIDIN-3-IL]-CYCLOPROPANECARBOXYLIC ACID AMIDE; N-[(2S,3R)-4,4-DIMETHYL-1-[1-(1-METHYL-6-OXO-1H-PYRIDIN-3-IL)-1H-INDAZOLE-5-IL]-5-OXO-2-PHENYL-PIR ROLIDIN-3-IL]-1-METHYL-1H-PYRAZOLE-3-CARBOXYLIC ACID AMIDE;AMIDA DEL ÁCIDO N-[(2S,3R)-4,4-DIMETIL-1-[1-(1-METIL-6-OXO-1H-PIRIDIN-3-IL)-1H-INDAZOL-5-IL]-5-OXO-2-FENIL-PIR ROLIDIN-3-IL]-5-METIL-[1,2,4]OXADIAZOL-3-CARBOXÍLICO; AMIDA DEL ÁCIDO N-[(2S,3R)-4,4-DIMETIL-1-[1-(1-METIL-6-OXO-1H-PIRIDIN-3-IL)-1H-INDAZOL-5-IL]-5-OXO-2-FENIL-PIR ROLIDIN-3-IL]-4-METIL-TIAZOL-5-CARBOXÍLICO; AMIDA DEL ÁCIDO N-[(2S,3R)-4,4-DIMETIL-1-[1-(1-METIL-6-OXO-1H-PIRIDIN-3-IL)-1H-INDAZOL-5-IL]-5-OXO-2-FENIL-PIR ROLIDIN-3-IL]-TIAZOL-4-CARBOXÍLICO; Y AMIDA DEL ÁCIDO N-[(2S,3R)-4,4-DIMETIL-1-[1-(1-METIL-6-OXO-1H-PIRIDIN-3-IL)-1H-INDAZOL-5-IL]-5-OXO-2-FENIL-PIR ROLIDIN-3-IL]-5-METIL-TIAZOL-4-CARBOXÍLICO.;